{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:50:27Z","timestamp":1791312627879,"version":"4.3.1"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Increased understanding of the functional complexity of the genome has led to growing recognition of the role of non-sequence-based regulatory variation in disorders of the human central nervous system. Most genomic analyses of the brain are limited by the use of bulk tissue, which comprises a heterogeneous mix of different neural cell types with distinct epigenetic profiles, thereby limiting the ability to attribute regulatory changes to specific cell populations. Given the limited availability of human post-mortem tissue resources and the importance of integrating multi-omic data from the same samples, there is a critical need for methods that enable parallel, cell-type\u2013resolved genomic profiling. We present optimised protocols using fluorescence-activated nuclei sorting (FANS) to isolate nuclei from different human and mouse brain cell types for downstream multi-omic analysis. Our approach enables the robust purification of neuronal, oligodendrocyte, microglial and other glial-origin nuclei from both adult and fetal brain tissue. We demonstrate that FANS-isolated nuclei are compatible with a wide range of genomic assays, including profiling of DNA modifications, histone modifications, chromatin accessibility, and gene expression. This protocol maximises the utility of limited post-mortem tissue resources and provides a unified workflow for comprehensive, cell-type\u2013specific interrogation of molecular mechanisms involved in the brain.<\/jats:p>","DOI":"10.1371\/journal.pone.0359643","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:52:55Z","timestamp":1791309175000},"page":"e0359643","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Optimised fluorescence-activated nuclei sorting for epigenomic analysis of cortical cell types"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3546-1726","authenticated-orcid":true,"given":"Barry","family":"Chioza","sequence":"first","affiliation":[{"name":"University of Exeter Medical School","place":["Exeter, United Kingdom"],"department":["Department of Clinical & Biomedical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Policicchio","sequence":"additional","affiliation":[{"name":"University of Exeter Medical School","place":["Exeter, United Kingdom"],"department":["Department of Clinical & Biomedical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Burrage","sequence":"additional","affiliation":[{"name":"University of Exeter Medical School","place":["Exeter, United Kingdom"],"department":["Department of Clinical & Biomedical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgina E. 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